Biphasic intraocular pressure response to calcitonin gene-related peptide

Purpose. To examine the effects of calcitonin gene-related peptide (CGRP) o n intraocular pressure (IOP). Methods. IOP was periodically measured in rabbits treated with intravitreal injection (20 mu l) of either: 1) CGRP (10(-4) similar to 10(-7) M) into o ne eye; 2) CGRP (10(-4) or 10(-6) M) into both eyes 30 min after intravitre al administration of CGRP-(8-37) (10(-3) M), a CGRP1 receptor antagonist, i nto one eye; 3) CGRP (10(-4) or 10(-6) M) into one eye 30 min after intrave nous administration (200 mg/kg) of either Nw-nitro-L-arginine methyl ester (L-NAME), a nonselective inhibitor of nitric oxide synthase (NOS), or amino guanidine (AG), a selective inhibitor of inducible NOS; or 4) CGRP (10(-4) or 10(-6) M) into one eye along with intraperitoneal indomethacin (50 mg/kg at -1 and 4 h). Results. CGRP (10(-4) and 10(-5) M) produced a biphasic IOP response, which consisted of an early ocular hypertensive phase and a subsequent sustained hypotensive phase. While CGRP (10(-6) NI) yielded only a profound IOP redu ction. CGRP-(8-37) significantly inhibited the IOP elevation induced by CGR P (10(-4) M) and completely abolished the IOP reduction induced by CGRP (10 (-6) M). The IOP increase induced by CGRP (10(-4) M) was completely abolish ed by L-NAME, but not affected by AG. The IOP reduction induced by CGRP (10 (-6) M) was not affected by L-NAME. Indomethacin did not significantly affe ct the IOP responses to CGRP. Conclusions. CGRP dose-dependently produces a biphasic IOP response, which is mediated by CGRP1 receptors. It is suggested that constitutive NOS is in volved in the early ocular hypertensive response.